Clinical and Genetic Reassessment in Patients With Clinically Diagnosed Hereditary Polyneuropathy

Hereditary polyneuropathy is a disabling condition with a genetic aetiology. However, genetic confirmation is not always attainable. This study aimed to assess the diagnostic clarification rate achieved through reassessment, including whole genome sequencing (WGS), in patients without confirmed genetic diagnoses.

We conducted a cross-sectional study using diagnosis codes to identify patients with hereditary polyneuropathy at a specialized neuromuscular center. Clinically diagnosed patients without genetic confirmation were invited to participate. They underwent neurological examination, composite scoring, extensive blood testing, and WGS. Based on the reassessment, patients were stratified into three groups: (1) genetic findings, (2) non-genetic aetiologies, and (3) no identified aetiology.

We screened 386 patient records; 66 patients were eligible, and 44 were included. Mean age at inclusion was 52.7 years, and mean age at symptom onset was 31.2 years. Reassessment identified six non-genetic etiologies, including treatable causes such as disc protrusion, systemic lupus, and chronic inflammatory demyelinating polyneuropathy. A relevant genetic variant was identified in 13 out of the 44 patients, yielding a genetic clarification rate of 30%. The most frequent genetic variant was the homozygous c.757del variant in SORD, found exclusively in patients with axonal neuropathy and teenage onset.

Reassessment clarified the diagnosis in 44% of clinically diagnosed patients with hereditary polyneuropathy (30% genetic, 14% non-genetic), underscoring the potential of reassessment in improving diagnostic precision.